Table 1.

Dual effect of nitric oxide (NO) and cyclic guanosine-3′,5′-monophosphate (cGMP) signaling in nociception.

Anti-nociceptive effects of nitric oxide signaling	Pro-nociceptive Effects of nitric oxide signaling
Increased NO/cGMP signaling yields anti-nociceptive responses to prostaglandin-E2 induced hyperalgesia119	NO contributes to development and maintenance of central sensitization115
Peripheral opioid analgesia is dependent on NO/cGMP signaling96	NO/cGMP signaling mediates glutamate induced hyperalgesia110
L-arginine increases mechanical thresholds in rats98	Neuronal NOS knockout mice show 50% reduction in thermal hyperalgesia and abolished mechanical hyperalgesia in models of inflammatory pain101
	NOS inhibition attenuates nerve-injury induced mechanical hyperalgesia102 and reduce thermal and mechanical hyperalgesia in inflammatory pain models97,103,104,112,127

NOS: nitric oxide synthase.